Structural and Functional Brain Changes in
Patients with Bipolar Disorder

by Lori Altshuler, M.D.

Bipolar disorder is a recurrent illness with high morbidity for some
patients. Episodes increase in frequency with time, and while a substantial
number of patients with bipolar disorder respond well to treatment and
live highly functional lives, approximately 10% to 15% of persons with
the illness have been described as consistently having poor social outcome
and poor response to treatment. Further, persistent cognitive deficits
have been reported in up to 30% of patients with bipolar disorder. These
data suggest that for some patients with the disorder, the illness may
not be benign, but may instead be associated with a deteriorative course.
The factors that contribute to this poorer outcome group have not yet
been elucidated.

The search for a neuroanatomic abnormality that may contribute to bipolar
illness is an area of great interest. Both structural and functional changes
in the brain are being studied with the hope that the data obtained will
help us further understand bipolar illness. While the discoveries made
thus far do not by themselves answer certain critical questions about
the illness (e.g. why the onset of symptoms occurs at a certain age in
life, why the illness is remitting in some persons and deteriorative in
others), continuing study of these changes provides information that allows
us to more selectively decide which questions to pursue and how best to
do so.

Post Mortem Research in Affective Disorder (Bipolar Disorder)
Very few systematic post mortem studies involving affective disorder patients
have been done. Until recently, most investigators doubted that an illness
marked by episodic dysfunctional periods alternating with periods of almost
total restitution of normal functioning could be associated with underlying
structural deficits in the brain. However, of the very few studies that
have been done, abnormalities in several brain regions have been observed.

COMPUTERIZED TOMOGRAPHY (CT)
In the last ten years structural brain changes have been demonstrated
by CT in a subset of hospitalized affective disorder patients. Lateral
ventricular enlargement or increased ventricular to brain ratios have
been most commonly reported. An example is shown in this journal. Enlarged
ventricles in particular have been a common finding seen in unipolar,
bipolar and schizophrenic patients. The ventricles in the brain are the
spaces where cerebrospinal fluid is stored. One explanation proposed for
enlarged

ventricles is that the brain tissue which previously occupied this space
has been somehow reduced. The tissue loss that might account for such
a finding has not been explored using the CT method due to its relatively
poor resolution.

MAGNETIC RESONANCE IMAGING (MRI)
Very few quantitative structural analyses using MRI have been reported
to date. Further, the affective state of the patients at the time of the
studies has been variable, making it difficult to assess if the finding
is related to a particular mood state in the illness or is present even
during euthymic periods. We and several other groups in the country have
begun to use MRI to explore differences in brain structure, assessing
in particular for reduced brain tissue that might account for enlarging
ventricles. Very preliminary data suggest temporal lobe volume reduction
in bipolar patients during well periods compared to normal controls. Other
groups have reported changes in subcortical structures (small structures
deep in the brain) in depressed patients compared to controls. The number
of patients in most of these studies is small and larger studies are in
progress.

Another abnormal finding in patients with bipolar disorder is the existence
of "bright white spots" (hyperintense areas in the brain) on
the MRI. Hyperintensities have been associated with a change in water
content of brain tissue at the location of the hyperintensity. Although
the cause of these areas of hyperintensities is not known for certain,
the presence of these bright white spots is more common in patients with
bipolar illness compared to controls. This finding suggests that there
may be brain differences in patients with bipolar illness compared to
normal controls.

COMBINING MRI STUDIES WITH NEUROPSYCHOLOGICAL TESTING
Our group is particularly interested in the possible impact of the frequency
and intensity of a patient's manic or depressive episodes on the patient's
brain structure (studied by MRI) and neuropsychological functioning (i.e.
cognitive functioning and memory deficits as rated by neuropsychological
testing). Unraveling these relationships could help to identify a subgroup
of bipolar patients that may be more vulnerable to relapse or who may
have
a more difficult course of illness.

It is possible, for example, that episodes of manias or depressions contribute
to changes in brain structure in some bipolar patients. Findings may vary
depending upon the particular symptoms experienced by the patient, and
the particular type of illness the patient has in the spectrum of bipolar
disorders. Such an investigation could yield important insights into the
etiology of the disorders. Longitudinal studies are needed to determine
the effects of illness episodes on brain structure. Unfortunately, there
have been very few such studies in mood disorder patients. One longitudinal
study using CT and having a mean follow up period of three years found
that a group of patients with affective disorder had significant progression
of ventricular enlargement in time compared to a schizophrenic and a normal
comparison group.

There are few studies of cognitive function and memory deficits in bipolar
patients in the euthymic state. Those that do exist suggest that a subgroup
of bipolar patients may continue to have subtle deficits in the euthymic
state that grow worse with time. The exact nature of the memory and cognitive
impairments remains to be determined and a correlation of these impairments
with changes in brain structure remains to be further demonstrated. Although
robust findings between structure and neuropsychological function have
been reported in schizophrenic patients, the relationship in bipolar patients
has not been well explored. (as of 1995, when this paper was written -
ed.)

CONCLUSION

Determining the relationships between episode frequency and number, and
changes in brain structure and function is essential to understanding
the etiology and course of bipolar disorder. To this end, our group is
currently pursuing longitudinal studies to assess if 1) there are brain
changes that occur in time with repeated episodes, and 2) if these repeated
episodes and brain structural changes are associated with decrement in
social or neuropsychological functioning.

LORI ALTSHULER, M.D. is an Assistant Clinical Professor of Psychiatry
at UCLANPI and a member of the research service of the Brentwood Veterans
Administration Medical Center.

Special thanks to California
NAMI. This article was originally published in The Journal of NAMI California,
and is provided on this web site with permission of NAMI California. Copyright
2000, NAMI California.

Disclaimer: The Bipolar Focus website
provides information about bipolar disorder to interested viewers. This information
is not a guide for patient treatment, nor is it meant to provide a substitute
for professional advice about medical treatment of the disorder by a licensed
physician or clinician. No medical advice is given, nor is any provided on or
distributed from this website. Users interested in medical advice or treatment
must consult a licensed practitioner. No doctor-patient relationship is created
through the use of this web site.